DIFFERENTIAL ANTAGONIST ACTIVITY OF ALPHA-HELICAL CORTICOTROPIN-RELEASING-FACTOR9-41 IN 3 BIOASSAY SYSTEMS

Studies were performed in conscious unrestrained rats to compare the ability of the CRF receptor antagonist, alpha-helical CRF9-41, to inhibit the actions of CRF in three in vivo bioassay systems. When both peptides were administered intracerebroventricularly, an antagonist:agonist ratio between 6:1-12:1 was required to abolish CRF-induced elevations of plasma catecholamine levels. When both peptides were administered iv, CRF-induced hypotension and tachycardia were completely prevented by an antagonist:agonist ratio of 6:1, whereas total blockade of CRF-induced elevations of plasma ACTH and beta-endorphin levels required an antagonist:agonist ratio of 3000:1. These results demonstrated marked differences in the ability of alpha-helical CRF9-41 to antagonize various biological actions of CRF and support the existence of multiple CRF receptor subtypes.